Systems for delivering injections into humans have been in use for many years. The most commonly used system is a hypodermic needle attached to an ampule. To perform an injection, the needle is inserted into the tissue to the desired depth and the operator simply depresses a plunger inside the ampule to deliver the injectate. Another method less commonly used is a needle-free injection system. These systems typically consist of a device and an ampule. The device generates the power and the ampule contains the injectate. The ampule typically has a circular opening at its distal end approximately 1/100.sup.th the size of its inside diameter. The device pushes the fluid out of this opening at speeds fast enough to penetrate the tissue and deposit the injectate. To perform this injection, the operator usually places the tip of the ampule against the skin of the patient and activates a trigger. For a needle-free injection system, the control of the depth of the injectate is done by the device, not the operator.
Parenteral (a route other than through the gastrointestinal tract) injections are classified according to five well established regions in which the injectate may be deposited. These are: intradermal (ID), subcutaneous (SC), intramuscular (IM), intravenous (IV)/Intraarterial (IA) and intramedullary (IMED). ID injections place the injectate in the skin or the intradermal space. SC injections place the injectate in the adipose (fat) tissue. IM injections place the injectate in the muscle. IV/IA injections place the injectate into a vein or artery. Lastly, IMED injections place the injectate in the bone marrow, spinal chord or in the medulla oblongata. Conventional needle and ampule systems can give injections in all five of these regions. Typically, needle-free injection systems are employed only for ID, SC and IM injections. The present invention relates to ID injections.
A needle and ampule system can be effective for many types of ID injectables (e.g. lidocaine) because when the correct technique is employed, it can inject a predetermined amount of fluid (typical volumes range from 0.1 to 0.3 cc). A proper ID injection will appear as a raised bump on the skin surface and appear whitish in color. This bump is usually referred to as a wheal. Administering a proper ID injection using a conventional needle and ampule injection system can be difficult. The space in which the tip of the needle must be placed is very small (about 1 mm). This space is usually referred to as the intradermal space, and is indicated schematically in FIGS. 1 and 2 at 2. The shaft of the needle 4 must be held at a very shallow angle with respect to the target surface, usually 5.degree. to 15.degree., and be held in a particular orientation. It is critical that the needle tip pass most of the way through the outer layer of skin, typically called the epidermis 5, but that the tip not penetrate the superficial fascia 6 (the tissue layer that separates the skin layer from the underlying adipose layer 8), or the volume of injectate 9 will not be delivered entirely in the intradermal space 2. Thus, an ID injection with a needle and ampule system requires an exacting technique from the user to give a proper injection. The clinician can determine whether a proper ID injection has been administered by lightly pressing on the wheal; if it disappears or flattens out, then the injection was not truly intradermal. If the needle penetrates the superficial fascia, the injectate will enter the adipose layer. This happens frequently with conventional ID injections and the only solution is to repeat the procedure until a satisfactory injection is given. This can be uncomfortable for the patient and frustrating for the clinician.
In the last few years, a substantial effort has been directed into the development of new types of vaccines and therapies. The term "Deoxyribonucleic Acid (DNA)-based injectables" refers to this new type of injectables. DNA is defined as a carrier of genetic information. Vaccines are defined as any preparation intended for active immunological prophylaxis (prevention of a disease). Therapies are defined as the treatment of a disease or disorder by various methods. DNA-based injectables promises to be an exciting new tool for the prevention and treatment of disease.
Briefly, the overall goal of an ID DNA-based injection is to prevent or treat disease. On a cellular level, the goal is to achieve transfection and expression. Transfection is defined as a method of gene transfer utilizing infection of a cell with nucleic acid (as from a retrovirus) resulting in subsequent viral replication in the transfected cell. Expression is defined as the cell's ability to produce the antigen. An antigen is any substance that, as a result of coming into contact with appropriate cells, induces a state of sensitivity and/or immune responsiveness after a latent period (days to weeks) and which reacts in a demonstrable way with antibodies and/or immune cells of the sensitized subject in vivo or in vitro. Transfection of DNA-based medications is enhanced by utilizing injection techniques that deposit the injectate over a large area at a sufficient pressure to ensure transfection, and cause a certain amount of local tissue disruption, encouraging an immune response. It is an object of the present invention to develop a needle-free injection system which is particularly suitable for ID DNA-based injectables.